PB1804: SLC7A11 IS A POTENTIAL THERAPEUTIC TARGET IN ACUTE MYELOID LEUKEMIA
Authors: Jiazheng LI, Luting Luo, Wanying Liu, Jianda Hu
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Acute myeloid leukemia (AML) is the most prevalent type of acute leukemia in adults. Solute Carrier Family 7 Member 11 (SLC7A11), a key molecule involved in ferroptosis, is a potential therapeutic target for cancer therapy. However, the effect and mechanism of SLC7A11 remains unknow in AML. Aims: We aimed to explore the prognostic value, biological function and correlation with immune infiltrating of SLC7A11 in AML through comprehensive bioinformatics analysis. Methods: The expression levels were explored using UCSC Xena and GEO dataset. TCGA dataset was used to assess the cytogenetic risk and prognostic effects with SLC7A11.The functional enrichment analysis of the differentially expressed genes (DEGs) between SLC7A11 low and SLC7A11 high was explored. Next, the protein-protein interaction (PPI) network was conducted by String database. The hub genes, screened by Cytohubba plugin of Cytoscoape were performed to analyze transcription factors (TFs) network and functional network analysis through NetworkAnalyst online database. Furthermore, we examined the enrichment of co-expressed genes in AML with SLC7A11 ultilizing the LinkedOmics database, and subsequently investigated the relationship between SLC7A11 and immune cell infiltration using ESTIMATE method in AML. After knokdown of SLC7A11 in THP1 and U937 AML cell lines, cell proliferation and drug sensitive of venetoclax was performed to discover biological function of SLC7A11 in AML. Results: SLC7A11 has been found to be significantly upregulated in the majority of tumors, including acute myeloid leukemia (AML), as verified by the GEO dataset. Notably, higher expression levels of SLC7A11 was associated with poor cytogenetic risk and overall survival. Next, we identified 1184 differentially expressed genes (DEGs) through high and low SLC7A11 expression groups. KEGG pathway enrichment analysis of these DEGs revealed their closely involvement in Cytokine-cytokine receptor interaction, Viral protein interaction with cytokine and cytokine receptor, Rap1 signaling pathway. Moreover, 10 hub genes screened by the String PPI network using Cytohubba plugin of Cytoscape. Subsequently, the NetworkAnalyst online tool showed hub genes transcription factors (TFs) network, drugs or other chemical substances network. Additionally, KEGG pathway enrichment analysis of the co-expression genes of SLC7A11 highlighted its association with crucial pathways such as Rap1 signaling pathway, Ferroptosis, and purine metabolism. Immune infiltrate analysis revealed SLC7A11 expression was positively correlated with NK cell resting, Eosinophils, Macrophages M0, Plasma cells and negatively correlated with Dendritic cell resting. In vitro experiments showed that knockdown SLC7A11 inhibited cell proliferation and decrease drug sensitive of venetoclax. Summary/Conclusion: SLC7A11 is contributed to AML progression, which can promote cell proliferation, increase drug sensitive of venetoclax and related to immune infiltrate. Thus, SLC7A11 may be a novel and potential target for AML patients. Keywords: AML